The long-term goals of this study are: (1) Alterations in drug-receptor interactions in the cholinergic system, membrane fluidity and membrane phospholipid-N-methyltransferases as a function of age in animals, and in ceroid-lipofuscin syndrome experimentally produced in tissues and membranes by peroxidation; (2) Variations in membrane phospholipid-N-methyltransferases and cytochrome P450 levels in liver microsomes of experimental animals as a function of age, and in regenerated liver cells in aged rats; and (3) Evaluation of drugs (e.g., Centrophenoxine) in aged rats and in experimental ceroid-lipofuscin syndrome for depletion of age pigments or protection against peroxidation. The following observations were made regarding rat hemidiaphragm as a function of age: (1) Muscle tension developed by electrical stimulation of the phrenic nerve or muscle decreased with increasing age; (2) In young rats (2-3 months), L-methionine increased the delta tension developed by stimulation of the phrenic nerve or the muscle. This methionine effect was blocked when S-adenosyl-L-homocysteine (SAH), an inhibitor of phospholipid methylation mediated by S-adenosyl-L-methionine (SAM) was increased in the muscle; (3) The methionine effect was erratic or insignificant in old rats (greater than 15 months). These observations indicate that SAM-mediated membrane phospholipid methylation and regulation of membrane fluidity may become defective with advancing age. The release of acetylcholine (ACH), spontaneously or upon electrical stimulation, from superfused rat cerebrum was lower in old rats (greater than 15 months) than in young rats (3 months). Choline uptake by the cerebral slices did not change with advancing age. These observations indicate that the ACH release mechanism (or the ACH synthetic pathway) becomes defective with age. Completion of these investigations may explain relationships between (1) muscle function, membrane phospholipid methylation and membrane fluidity, and (2) enzymes of the ACH synthetic pathway and mechanisms of ACH release as a function of age.